Alpha sarcin is a ribonuclease that cleaves the phosphodiester bond on the 3' side of G4325 in 28S rRNA; ricin A-chain is a RNA N-glycosidase that depurinates the 5' adjacent A4324. These single covalent modifications inactivate the ribosomes. An oligoribonucleotide that reproduces the structure of the sarcin/ricin domain in 28S rRNA was synthesized and mutations were constructed in the 3'C and the 5'G that surround the GAGA tetrad that has the site of toxin action. Analysis indicates that catalysis by ricin requires a Watson-Crick pair to shut off a putative GAGA tetraloop, whereas, alpha sarcin does not. One interpretation is that there are alternate conformations of the sarcin/ricin domain in 28S rRNA and that one of the conformers is recognized by sarcin and the other by ricin A-chain. This switch in the structure could underlie the translocation of peptidyl-tRNA from the A to the P site and the vectoral displacement of mRNA one codon during elongation.